POS0081 LONG-TERM EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS: 2-YEAR RESULTS FROM THE PHASE 3 SELECT-PsA 1 STUDY
Authors: I. Mcinnes, K. Kato, M. Magrey, J. F. Merola, M. Kishimoto, D. Haaland, L. Chen, Y. Duan, J. Liu, R. Lippe, P. Wung
Journal: Annals of the Rheumatic Diseases (2022)

Background In SELECT-PsA 1, patients (pts) with psoriatic arthritis (PsA) and an inadequate response or intolerance to ≥1 non-biologic disease-modifying antirheumatic drug showed improvement in the signs and symptoms of PsA with upadacitinib 15 mg (UPA15) or 30 mg (UPA30), an oral Janus kinase (JAK) inhibitor, through week (wk) 56. 1 Objectives To evaluate the efficacy and safety of UPA and UPA vs adalimumab (ADA) at wk 104 from the ongoing long-term extension of SELECT-PsA 1. Methods Pts received UPA15, UPA30, ADA 40 mg, or placebo (PBO) for 24 wks, at which point, PBO pts switched to UPA15 or UPA30. Efficacy endpoints were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures and AO (continuous endpoints), with nominal P -values shown, for continuous UPA and ADA treatment groups. Treatment-emergent adverse events were summarized for pts who received ≥1 dose of study drug using a visit-based cut-off at wk 104. Results 1704 pts received ≥1 dose of study drug. At wk 104, 25.4% of patients had discontinued study drug. The proportions of pts who achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of enthesitis or dactylitis showed consistent responses, or further improvements, from wk 56 1 to wk 104 (Table 1). ACR20/50/70 and MDA responses, as well as mean change from baseline (BL) in HAQ-DI, patient’s assessment of pain, BASDAI, and ASDAS, were greater with UPA vs ADA. Mean change from BL in modified total Sharp/van der Heijde Score (mTSS) was generally similar across groups and comparable to wk 56. 1 The safety profile of UPA was generally comparable to ADA (Figure 1) and consistent with wk 56 1 data. Rates of serious infection, herpes zoster, lymphopenia, and elevated CPK remained numerically higher with UPA30 vs UPA15; rates in both UPA groups were higher vs ADA. Rates of malignancies, MACE, or VTE were similar across groups, and consistent with wk 56 1 data. Two deaths were reported with UPA15, 1 with UPA30, and 1 with ADA. Table 1. Efficacy Endpoints at Week 104 Endpoint UPA15(n=429) UPA30(n=423) ADA(n=429) Proportion of Pts (%) a NRI AO NRI AO NRI AO ACR20 69.0 87.9 69.5 87.9 63.4 85.1 ACR50 53.6 67.4 59.3* 74.1 47.1 62.3 ACR70 38.0* 47.4 43.5* 54.4 29.4 39.1 Minimal Disease Activity (MDA) 42.0 54.8 45.9* 56.8 37.8 50.3 PASI75 b 57.9 73.4 62.4 78.6 58.8 76.5 PASI90 b 46.7 59.0 53.3 66.5 48.8 63.3 PASI100 b 34.1 43.4 42.4 51.4 34.1 44.0 Resolution of enthesitis by LEI c 53.3 75.5 52.2 72.0 49.1 73.9 Resolution of dactylitis by LDI d 69.9 94.5 71.7 96.2 72.4 95.2 Change from BL e MMRM AO MMRM AO MMRM AO Health Assessment Questionnaire - Disability Index (HAQ-DI) -0.55* -0.57 -0.55* -0.59 -0.45 -0.47 Patient’s assessment of pain (numeric rating scale) -3.3 -3.5 -3.4* -3.6 -3.0 -3.2 Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) f -3.0 -3.2 -3.3 -3.6 -2.7 -2.6 Ankylosing Spondylitis Disease Activity Score (ASDAS) f -1.6 -1.8 -1.9* -2.1 -1.5 -1.6 Modified total Sharp/van der Heijde Score (mTSS) 0.03 0.01 0.01 0.00 0.11 0.11 ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology criteria; ADA, adalimumab; AO, as observed; BL, baseline; LDI, Leeds Dactylitis Index; LEI, Leeds Enthesitis Index; MMRM, mixed effect model repeated measurement; NRI, non-responder imputation; PASI75/90/100, ≥75%/90%/100% improvement in Psoriasis Area and Severity Index; pts, patients; UPA, upadacitinib. a Data shown as NRI and AO for binary endpoints. b For pts with psoriasis affecting ≥3% of body surface area at BL. c For pts with LEI &gt;0 at BL; resolution LEI=0. d For pts with LDI &gt;0 at BL; resolution LDI=0. e Data shown as MMRM (LS mean) and AO (mean) for continuous endpoints. f For pts with psoriatic spondylitis at BL. Nominal * P &lt;0.05, UPA15 or UPA30 vs ADA for NRI and MMRM; AO descriptive only. Conclusion In PsA pts, efficacy responses were similar or greater with UPA15 or UPA30 vs ADA at wk 104, and inhibition of radiographic progression was maintained. No new safety signals were identified with long-term exposure to UPA up to 2 years. References [1]McInnes I, et al. RMD Open , 2021; 7(3):e001838. Acknowledgements AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial ( NCT03104400 ). AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Monica R.P. Elmore, PhD of AbbVie. Disclosure of Interests Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, and UCB Pharma, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, and UCB Pharma, Koji Kato Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: Employee of AbbVie, Marina Magrey Consultant of: UCB, Novartis, Eli Lilly, Pfizer, and Janssen, Grant/research support from: Amgen, AbbVie, and UCB Pharma, Joseph F. Merola Consultant of: Merck, Bristol-Myers Squibb, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres, and Leo Pharma, Mitsumasa Kishimoto Consultant of: AbbVie, Amgen-Astellas BioPharma, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Celgene, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, Teijin Pharma, and UCB Pharma, Derek Haaland Speakers bureau: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, Consultant of: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Eli-Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, UCB, Grant/research support from: AbbVie, Adiga Life-Sciences, Amgen, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Eli-Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Regeneron, Sanofi-Genzyme, UCB, Liang Chen Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: Employee of AbbVie, Yuanyuan Duan Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: Employee of AbbVie, Jianzhong Liu Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: Employee of AbbVie, Ralph Lippe Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: Employee of AbbVie, Peter Wung Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: Employee of AbbVie